title: Increased production of IL-6 and IL-17 in lipopolysaccharide-stimulated peripheral mononuclears from patients with rheumatoid arthritis.
abstract: TLR4-mediated inflammatory responses are important for innate immune functions, thus their alterations may participate in the pathogenesis of rheumatoid arthritis (RA). Cortisol is one of the most potent immunomodulatory hormones involved in control of inflammation. In this study, we analyzed TLR4-mediated responses and cortisol effects on the process in peripheral blood mononuclear cells (PBMC) from RA patients. Lipopolysaccharide-stimulated PBMC from 23 female patients and 15 healthy controls were cultured in the presence or absence of cortisol (1 μM) for 24 h. A panel of 17 inflammatory cytokines was analyzed in the cell culture supernatants. Higher (p < 0.05) concentrations of IL-6, IL-17 and MCP-1 were found in lipopolysaccharide-stimulated PBMC from RA patients compared to controls. After normalization of stimulated cytokine secretion to unstimulated cells, a significantly higher (p < 0.05) IL-6 and G-CSF production was found in RA PBMC. Cortisol induced stronger (p < 0.05) suppression of lipopolysaccharide-stimulated secretion of IL-1β, IL-6, IL-17 and G-CSF in RA group compared to controls. The observed higher production of the key inflammatory cytokines by RA PBMC to lipopolysaccharide stimulation supports involvement of TLR4-mediated processes in RA pathogenesis. The higher sensitivity of LPS-stimulated RA PBMC to immunosuppressive effects of cortisol may reflect adaptive processes to chronic inflammation.
authors.affiliation: Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
authors.forename: Lucia
authors.initials: L
authors.lastname: Chovanova
authors.forename: Miroslav
authors.initials: M
authors.lastname: Vlcek
authors.forename: Katarina
authors.initials: K
authors.lastname: Krskova
authors.forename: Adela
authors.initials: A
authors.lastname: Penesova
authors.forename: Zofia
authors.initials: Z
authors.lastname: Radikova
authors.forename: Jozef
authors.initials: J
authors.lastname: Rovensky
authors.forename: Dana
authors.initials: D
authors.lastname: Cholujova
authors.forename: Jan
authors.initials: J
authors.lastname: Sedlak
authors.forename: Richard
authors.initials: R
authors.lastname: Imrich
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D056747:Immunomodulation / Q000187:drug effects; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D020381:Interleukin-17; D015850:Interleukin-6; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D006854:Hydrocortisone